Generic placeholder image

Current Proteomics


ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Research Article

Characterization of Venoms of Deinagkistrodon acutus and Bungarus multicinctus Using Proteomics and Peptidomics

Author(s): Yaqiong Zhang, Zhiping Jia, Yunyang Liu, Xinwen Zhou and Yi Kong*

Volume 17, Issue 3, 2020

Page: [241 - 254] Pages: 14

DOI: 10.2174/1570164617666191121112319

Price: $65


Background: Deinagkistrodon acutus (D. acutus) and Bungarus multicinctus (B. multicinctus) as traditional medicines have been used for hundreds of years in China. The venoms of these two species have strong toxicity on the victims.

Objective: The objective of this study is to reveal the profile of venom proteins and peptides of D. acutus and B. multicinctus.

Methods: Ultrafiltration, SDS-PAGE coupled with in-gel tryptic digestion and Liquid Chromatography- Electrospray Ionization-Tandem Mass Spectrometry (LC-ESI-MS/MS) were used to characterize proteins and peptides of venoms of D. acutus and B. multicinctus.

Results: In the D. acutus venom, 67 proteins (16 protein families) were identified, and snake venom metalloproteinases (SVMPs, 38.0%) and snake venom C-type lectins (snaclecs, 36.7%) were dominated proteins. In the B. multicinctus venom, 47 proteins (15 protein families) were identified, and three-finger toxins (3FTxs, 36.3%) and Kunitz-type Serine Protease Inhibitors (KSPIs, 32.8%) were major components. In addition, both venoms contained small amounts of other proteins, such as Snake Venom Serine Proteinases (SVSPs), Phospholipases A2 (PLA2s), Cysteine-Rich Secreted Proteins (CRISPs), 5'nucleotidases (5'NUCs), Phospholipases B (PLBs), Phosphodiesterases (PDEs), Phospholipase A2 Inhibitors (PLIs), Dipeptidyl Peptidases IV (DPP IVs), L-amino Acid Oxidases (LAAOs) and Angiotensin-Converting Enzymes (ACEs). Each venom also had its unique proteins, Nerve Growth Factors (NGFs) and Hyaluronidases (HYs) in D. acutus, and Cobra Venom Factors (CVFs) in B. multicinctus. In the peptidomics, 1543 and 250 peptides were identified in the venoms of D. acutus and B. multicinctus, respectively. Some peptides showed high similarity with neuropeptides, ACE inhibitory peptides, Bradykinin- Potentiating Peptides (BPPs), LAAOs and movement related peptides.

Conclusion: Characterization of venom proteins and peptides of D. acutus and B. multicinctus will be helpful for the treatment of envenomation and drug discovery.

Keywords: Deinagkistrodon acutus, Bungarus multicinctus, proteomics, peptidomics, snake venom metalloproteinases, threefinger toxins.

« Previous
Graphical Abstract
Warrell, D.A. Venomous bites, stings, and poisoning. Infect. Dis. Clin. North Am., 2012, 26(2), 207-223.
[] [PMID: 22632635]
Gutiérrez, J.M.; Calvete, J.J.; Habib, A.G.; Harrison, R.A.; Williams, D.J.; Warrell, D.A. Snakebite envenoming. Nat. Rev. Dis. Primers, 2017, 3, 17063.
[] [PMID: 28905944]
Cheng, C.L.; Mao, Y.C.; Liu, P.Y.; Chiang, L.C.; Liao, S.C.; Yang, C.C. Deinagkistrodon acutus envenomation: a report of three cases. J. Venom. Anim. Toxins Incl. Trop. Dis., 2017, 23, 20.
[] [PMID: 28344596]
Kasturiratne, A.; Wickremasinghe, A.R.; de Silva, N.; Gunawardena, N.K.; Pathmeswaran, A.; Premaratna, R.; Savioli, L.; Lalloo, D.G.; de Silva, H.J. The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med., 2008, 5(11)e218
[] [PMID: 18986210]
Kulawickrama, S.; O’Leary, M.A.; Hodgson, W.C.; Brown, S.G.; Jacoby, T.; Davern, K.; Isbister, G.K. Development of a sensitive enzyme immunoassay for measuring taipan venom in serum. Toxicon, 2010, 55(8), 1510-1518.
[] [PMID: 20223258]
Calvete, J.J.; Sanz, L.; Angulo, Y.; Lomonte, B.; Gutiérrez, J.M. Venoms, venomics, antivenomics. FEBS Lett., 2009, 583(11), 1736-1743.
[] [PMID: 19303875]
Ziganshin, R.H.; Kovalchuk, S.I.; Arapidi, G.P.; Starkov, V.G.; Hoang, A.N.; Thi Nguyen, T.T.; Nguyen, K.C.; Shoibonov, B.B.; Tsetlin, V.I.; Utkin, Y.N. Quantitative proteomic analysis of Vietnamese krait venoms: neurotoxins are the major components in Bungarus multicinctus and phospholipases A2 in Bungarus fasciatus. Toxicon,, 2015, 107(Pt B), 197-209.
[] [PMID: 26341420]
Shan, L.L.; Gao, J.F.; Zhang, Y.X.; Shen, S.S.; He, Y.; Wang, J.; Ma, X.M.; Ji, X. Proteomic characterization and comparison of venoms from two elapid snakes (Bungarus multicinctus and Naja atra) from China. J. Proteomics, 2016, 138, 83-94.
[] [PMID: 26924299]
Liu, C.C.; Lin, C.C.; Hsiao, Y.C.; Wang, P.J.; Yu, J.S. Proteomic characterization of six Taiwanese snake venoms: identification of species-specific proteins and development of a SISCAPA-MRM assay for cobra venom factors. J. Proteomics, 2018, 187, 59-68.
[] [PMID: 29929037]
Chen, P.C.; Huang, M.N.; Chang, J.F.; Liu, C.C.; Chen, C.K.; Hsieh, C.H. Snake venom proteome and immuno-profiling of the hundred-pace viper, Deinagkistrodon acutus, in Taiwan. Acta Trop., 2019, 189, 137-144.
[] [PMID: 30268686]
Schrader, M.; Schulz-Knappe, P. Peptidomics technologies for human body fluids. Trends Biotechnol., 2001, 19(10)(Suppl.), S55-S60.
[] [PMID: 11780972]
Munawar, A.; Trusch, M.; Georgieva, D.; Spencer, P.; Frochaux, V.; Harder, S.; Arni, R.K.; Duhalov, D.; Genov, N.; Schlüter, H.; Betzel, C. Venom peptide analysis of Vipera ammodytes meridionalis (Viperinae) and Bothrops jararacussu (Crotalinae) demonstrates subfamily-specificity of the peptidome in the family Viperidae. Mol. Biosyst., 2011, 7(12), 3298-3307.
[] [PMID: 21959992]
Bocian, A.; Urbanik, M.; Hus, K.; Łyskowski, A.; Petrilla, V.; Andrejčáková, Z.; Petrillová, M.; Legath, J. Proteome and Peptidome of Vipera berus berus Venom. Molecules, 2016, 21(10), 21.
[] [PMID: 27775574]
Degueldre, M.; Echterbille, J.; Smargiasso, N.; Damblon, C.; Gouin, C.; Mourier, G.; Gilles, N.; De Pauw, E.; Quinton, L. In-depth glyco-peptidomics approach reveals unexpected diversity of glycosylated peptides and atypical post-translational modifications in Dendroaspis angusticeps snake venom. Int. J. Mol. Sci., 2017, 18(11), 18.
[] [PMID: 29156586]
Gutiérrez, J.M.; Escalante, T.; Rucavado, A.; Herrera, C. Hemorrhage caused by snake venom metalloproteinases: a journey of discovery and understanding. Toxins (Basel), 2016, 8(4), 93.
[] [PMID: 27023608]
de Queiroz, M.R.; de Sousa, B.B.; da Cunha Pereira, D.F.; Mamede, C.C.N.; Matias, M.S.; de Morais, N.C.G.; de Oliveira Costa, J.; de Oliveira, F. The role of platelets in hemostasis and the effects of snake venom toxins on platelet function. Toxicon, 2017, 133, 33-47.
[] [PMID: 28435120]
Arlinghaus, F.T.; Eble, J.A. C-type lectin-like proteins from snake venoms. Toxicon, 2012, 60(4), 512-519.
[] [PMID: 22781131]
Tan, C.H.; Tan, K.Y.; Lim, S.E.; Tan, N.H. Venomics of the beaked sea snake, Hydrophis schistosus: a minimalist toxin arsenal and its cross-neutralization by heterologous antivenoms. J. Proteomics, 2015, 126, 121-130.
[] [PMID: 26047715]
Jiang, Y.; Li, Y.; Lee, W.; Xu, X.; Zhang, Y.; Zhao, R.; Zhang, Y.; Wang, W. Venom gland transcriptomes of two elapid snakes (Bungarus multicinctus and Naja atra) and evolution of toxin genes. BMC Genomics, 2011, 12, 1.
[] [PMID: 21194499]
Chanda, C.; Sarkar, A.; Sistla, S.; Chakrabarty, D. Anti-platelet activity of a three-finger toxin (3FTx) from Indian monocled cobra (Naja kaouthia) venom. Biochem. Biophys. Res. Commun., 2013, 441(3), 550-554.
[] [PMID: 24183721]
Mukherjee, A.K.; Mackessy, S.P.; Dutta, S. Characterization of a Kunitz-type protease inhibitor peptide (Rusvikunin) purified from Daboia russelii russelii venom. Int. J. Biol. Macromol., 2014, 67, 154-162.
[] [PMID: 24632346]
Serrano, S.M. The long road of research on snake venom serine proteinases. Toxicon, 2013, 62, 19-26.
[] [PMID: 23010164]
Serrano, S.M.; Maroun, R.C. Snake venom serine proteinases: sequence homology vs. substrate specificity, a paradox to be solved. Toxicon, 2005, 45(8), 1115-1132.
[] [PMID: 15922778]
Cohen, D.J.; Maldera, J.A.; Vasen, G.; Ernesto, J.I.; Muñoz, M.W.; Battistone, M.A.; Cuasnicú, P.S. Epididymal protein CRISP1 plays different roles during the fertilization process. J. Androl., 2011, 32(6), 672-678.
[] [PMID: 21441424]
Guo, M.; Teng, M.; Niu, L.; Liu, Q.; Huang, Q.; Hao, Q. Crystal structure of the cysteine-rich secretory protein stecrisp reveals that the cysteine-rich domain has a K+ channel inhibitor-like fold. J. Biol. Chem., 2005, 280(13), 12405-12412.
[] [PMID: 15596436]
Yamazaki, Y.; Morita, T. Structure and function of snake venom cysteine-rich secretory proteins. Toxicon, 2004, 44(3), 227-231.
[] [PMID: 15302528]
Dhananjaya, B.L.; D’Souza, C.J. The pharmacological role of nucleotidases in snake venoms. Cell Biochem. Funct., 2010, 28(3), 171-177.
[] [PMID: 20186872]
Chapeaurouge, A.; Reza, M.A.; Mackessy, S.P.; Carvalho, P.C.; Valente, R.H.; Teixeira-Ferreira, A.; Perales, J.; Lin, Q.; Kini, R.M. Interrogating the venom of the viperid snake Sistrurus catenatus edwardsii by a combined approach of electrospray and MALDI mass spectrometry. PLoS One, 2015, 10(5)e0092091
[] [PMID: 25955844]
Trummal, K.; Aaspõllu, A.; Tõnismägi, K.; Samel, M.; Subbi, J.; Siigur, J.; Siigur, E. Phosphodiesterase from Vipera lebetina venom - structure and characterization. Biochimie, 2014, 106, 48-55.
[] [PMID: 25079051]
Choudhury, M.; McCleary, R.J.R.; Kesherwani, M.; Kini, R.M.; Velmurugan, D. Comparison of proteomic profiles of the venoms of two of the ‘Big Four’ snakes of India, the Indian cobra (Naja naja) and the common krait (Bungarus caeruleus), and analyses of their toxins. Toxicon, 2017, 135, 33-42.
[] [PMID: 28602829]
Estevão-Costa, M.I.; Rocha, B.C.; de Alvarenga Mudado, M.; Redondo, R.; Franco, G.R.; Fortes-Dias, C.L. Prospection, structural analysis and phylogenetic relationships of endogenous gamma-phospholipase A(2) inhibitors in Brazilian Bothrops snakes (Viperidae, Crotalinae). Toxicon, 2008, 52(1), 122-129.
[] [PMID: 18620721]
Slimane, T.A.; Lenoir, C.; Sapin, C.; Maurice, M.; Trugnan, G. Apical secretion and sialylation of soluble dipeptidyl peptidase IV are two related events. Exp. Cell Res., 2000, 258(1), 184-194.
[] [PMID: 10912800]
Aird, S.D. Snake venom dipeptidyl peptidase IV: taxonomic distribution and quantitative variation. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2008, 150(2), 222-228.
[] [PMID: 18440846]
Samel, M.; Tõnismägi, K.; Rönnholm, G.; Vija, H.; Siigur, J.; Kalkkinen, N.; Siigur, E. L-Amino acid oxidase from Naja naja oxiana venom. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2008, 149(4), 572-580.
[] [PMID: 18294891]
Yap, M.K.; Fung, S.Y.; Tan, K.Y.; Tan, N.H. Proteomic characterization of venom of the medically important Southeast Asian Naja sumatrana (Equatorial spitting cobra). Acta Trop., 2014, 133, 15-25.
[] [PMID: 24508616]
Malih, I. Ahmad rusmili, M.R.; Tee, T.Y.; Saile, R.; Ghalim, N.; Othman, I. Proteomic analysis of Moroccan cobra Naja haje legionis venom using tandem mass spectrometry. J. Proteomics, 2014, 96, 240-252.
[] [PMID: 24269350]
Huang, H.W.; Liu, B.S.; Chien, K.Y.; Chiang, L.C.; Huang, S.Y.; Sung, W.C.; Wu, W.G. Cobra venom proteome and glycome determined from individual snakes of Naja atra reveal medically important dynamic range and systematic geographic variation. J. Proteomics, 2015, 128, 92-104.
[] [PMID: 26196238]
Zhao, Y.; Li, B.; Dong, S.; Liu, Z.; Zhao, X.; Wang, J.; Zeng, M. A novel ACE inhibitory peptide isolated from Acaudina molpadioidea hydrolysate. Peptides, 2009, 30(6), 1028-1033.
[] [PMID: 19463733]
Dutta, S.; Chanda, A.; Kalita, B.; Islam, T.; Patra, A.; Mukherjee, A.K. Proteomic analysis to unravel the complex venom proteome of Eastern India Naja naja: correlation of venom composition with its biochemical and pharmacological properties. J. Proteomics, 2017, 156, 29-39.
[] [PMID: 28062377]
Tan, K.Y.; Tan, C.H.; Chanhome, L.; Tan, N.H. Comparative venom gland transcriptomics of Naja kaouthia (monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty. PeerJ, 2017, 5e3142
[] [PMID: 28392982]
Wahby, A.F.; Mahdy, S.M.; El-Mezayen, H.A.; Salama, W.H.; Abdel-Aty, A.M.; Fahmy, A.S. Egyptian horned viper Cerastes cerastes venom hyaluronidase: purification, partial characterization and evidence for its action as a spreading factor. Toxicon, 2012, 60(8), 1380-1389.
[] [PMID: 23000079]
Chong, H.P.; Tan, K.Y.; Tan, N.H.; Tan, C.H. Exploring the diversity and novelty of toxin genes in Naja sumatrana, the Equatorial Spitting Cobra from Malaysia through De Novo venom-gland transcriptomics. Toxins (Basel), 2019, 11(2), 11.
[] [PMID: 30754700]
Shtatland, T.; Guettler, D.; Kossodo, M.; Pivovarov, M.; Weissleder, R. PepBank--a database of peptides based on sequence text mining and public peptide data sources. BMC Bioinformatics, 2007, 8, 280.
[] [PMID: 17678535]
Gäde, G. A unique charged tyrosine-containing member of the adipokinetic hormone/red-pigment-concentrating hormone peptide family isolated and sequenced from two beetle species. Biochem. J., 1991, 275(Pt 3), 671-677.
[] [PMID: 2039445]
Borovsky, D. Trypsin-modulating oostatic factor: a potential new larvicide for mosquito control. J. Exp. Biol., 2003, 206(Pt 21), 3869-3875.
[] [PMID: 14506222]
Tashima, A.K.; Zelanis, A.; Kitano, E.S.; Ianzer, D.; Melo, R.L.; Rioli, V.; Sant’anna, S.S.; Schenberg, A.C.; Camargo, A.C.; Serrano, S.M. Peptidomics of three Bothrops snake venoms: insights into the molecular diversification of proteomes and peptidomes. Mol. Cell. Proteomics, 2012, 11(11), 1245-1262.
[] [PMID: 22869554]
Ianzer, D.; Konno, K.; Marques-Porto, R.; Vieira Portaro, F.C.; Stöcklin, R.; Martins de Camargo, A.C.; Pimenta, D.C. Identification of five new Bradykinin Potentiating Peptides (BPPs) from Bothrops jararaca crude venom by using electrospray ionization tandem mass spectrometry after a two-step liquid chromatography. Peptides, 2004, 25(7), 1085-1092.
[] [PMID: 15245866]
Giacometti, J.; Buretić-Tomljanović, A. Peptidomics as a tool for characterizing bioactive milk peptides. Food Chem., 2017, 230, 91-98.
[] [PMID: 28407976]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy